Cytokine-, stress-, and oncoprotein-activated human protein kinase kinases

Abstract

Disclosed are human mitogen-activated (MAP) kinase kinase isoforms (MKKs). MKKs mediate unique signal transduction pathways that activate human MAP kinases p38 and JNK, which result in activation of other factors, including activating transcription factor-2 (ATF2) and c-Jun. The pathways are activated by a number of factors, including cytokines and environmental stress. Methods are provided for identifying reagents that modulate MKK function or activity and for the use of such reagents in the treatment of MKK-mediated disorders.

What is claimed is:  
     
       1. A substantially pure human mitogen-activated protein kinase kinase (MKK) polypeptide having serine, theonine, and tyrosine kinase activity, and phosphorylating human mitogen-activated protein (MAP) kinase p38comprising the amino acid sequence of SEQ ID NO:2. 
     
     
       2. A substantially pure human mitogen-activated protein kinase kinase (MKK) polypeptide having serine, theonine, and tyrosine kinase activity, and phosphorylating human mitogen-activated protein (MAP) kinase p38 comprising the amino acid sequence of SEQ ID NO:4. 
     
     
       3. A substantially pure human mitogen-activated protein kinase kinase (MKK) polypeptide having serine, threonine, and tyrosine kinase activity, and phosphorylating human mitogen-activated protein (MAP) kinase p38, further characterized in that the polypeptide phosphorylates human mitogen-activated protein (MAP) kinase JNK comprising the amino acid sequence of SEQ ID NO:6. 
     
     
       4. A substantially pure human mitogen-activated protein kinase kinase (MKK) polypeptide having serine, threonine, and tyrosine kinase activity, and phosphorylating human mitogen-activated protein (MAP) kinase p38, further characterized in that the polypeptide phosphorylates human mitogen-activated protein (MAP) kinase JNK comprising the amino acid sequence of SEQ ID NO:8. 
     
     
       5. A substantially pure human mitogen-activated protein kinase kinase (MKK) polypeptide having serine, threonine, and tyrosine kinase activity, and phosphorylating human mitogen-activated protein (MAP) kinase p38, further characterized in that the polypeptide phosphorylates human mitogen-activated protein (MAP) kinase JNK comprising the amino acid sequence of SEQ ID NO:10. 
     
     
       6. A purified antibody which binds specifically to a polypeptide of  claim 1 . 
     
     
       7. A purified antibody which binds specifically to a polypeptide of  claim 2 . 
     
     
       8. A purified antibody which binds specifically to a polypeptide of  claim 3 . 
     
     
       9. A purified antibody which binds specifically to a polypeptide of  claim 4 . 
     
     
       10. A purified antibody which binds specifically to a polypeptide of  claim 5 .